javad baharara

In recent years, nanoparticles have gained increasing popularity over traditional physicochemical methods for fighting pathogenic microorganisms. Due to their unique properties, cerium oxide nanoparticles (CeO2 NPs) have recently emerged as a promising candidate for biomedical applications.

This study aimed to investigate the antibacterial effects of CeO2 NPs prepared using alginate, following the disc diffusion method.

For this purpose, four bacterial strains were used in this study: two Gram-positive [Bacillus subtilis (PTCC 1365) and Staphylococcus aureus ATCC 25923] and two Gram-negative [Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 9027]. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were measured using the microdilution method, and the anti-biofilm activity of the synthetic material was also assessed.

The results demonstrated the inhibitory effects of the synthesized nanoparticles on gram-positive bacteria, with significant growth inhibition observed in S. aureus and B. subtilis, after exposure to CeO2 NPs.

CeO2 NPs synthesized by alginate exhibited significant antibacterial effects against Gram-positive bacteria and could disrupt biofilm structure and prevent further biofilm formation. The findings highlight the potential of CeO2 NPs synthesized by alginate as a novel antibacterial and anti-biofilm therapeutic agent.

Granulosa cell tumor (GCT) is a sex cord-stromal rare malignancy; and is associated with infertility. Extracellular vesicles (EVs) are small secreted vesicles containing proteins, mRNA, and miRNA, therefore modulating signaling pathways potentially in recipient cells and in this way, they can help cancer spread through intercellular communication. In this research, the capability of ovarian cancer-derived EVs for inducing proliferation and metastasis in GCs is investigated. In the experimental study, EVs were isolated by ultracentrifugation from A2780 human ovarian cancer cell-conditioned. Mouse GCs were mechanically isolated from 8 female mice. ovarian cancer-derived EVs were then added to the GCs (experimental groups: untreated GCs (control group), GCs treated with concentrations of 10, 25, and 50 μg/ml), and cell viability, migration, apoptosis, and estrogen hormone measurements were assessed by MTT, scratch assay, propidium iodide (PI) staining, annexin-V-FITC/PI and ELISA assay respectively. Gene's expression of Amh, Foxl2, Gdf-9, and Igf-1r were determined using real-time polymerase chain reaction (PCR). GCs treated with ovarian cancer EVs indicate an increase in cell viability compared to the control cells (P<0.05). Also, ovarian cancer EVs showed an increase in the migration potency. The other results this experimental study showed that ovarian cancer EVs increase in the estrogen secretion level (P<0.001) and reduce the apoptosis of GCs compared to the control group. It is further showed that EVs isolated from ovarian cancer (A2780 cell line) can induce the RNA expression level of several genes in recipient GCs, such as Amh, Foxl2, and Igf-1r (P<0.01, P<0.001), respectively, while the RNA expression level of Gdf-9 gene was decreased in comparison with the control. To sum up, the research here provides a novel insight into the role of ovarian cancer EVs in proliferation and metastasis in GCs and prevention of infertility caused by granulosa cancer.

Intestinal colitis or ulcerative colitis is an inflammatory bowel disease that causes long-term inflammation and ulcers in the gastrointestinal tract. It has been suggested that mucosal expression of angiotensin II (AT-II) is increased in colitis. Here, we examined the potential therapeutic effects of combination therapy regarding Enalapril, as an Angiotensin-converting enzyme inhibitor, with sulfasalazine (SSZ) in a murine colitis model.

Male C57BL/6 mice divided to five groups: control group (distilled water), dextran sulphate sodium (DSS) (colitis group) (1 % DSS), SSZ (positive control group) with 100 mg/ kg/day, Enalapril alone group with 4 mg/kg/day, Enalapril (4 mg/kg/day) + SSZ (100 mg/kg/day).

There was a significant reduction in disease activity index among the group of mice receiving the combination of Enalapril and SSZ compared to the colitis group. Enalapril and SSZ treatment was associated with a lower reduction in colon length, decreased colon weight, spleen weight and spleen-to-body weight in mice with colitis. Following DSS administration, Enalapril and SSZ also significantly decreased MDA levels as an oxidant marker, and increased total thiol, SOD, and CAT levels, as anti-oxidants. In addition, mucosal damage, crypt loss, pathological changes, and inflammation score decreased after treatment with Enalapril and SSZ in comparison with colitis group. The combination of Enalapril and SSZ reduced colon collagen content and caused fibrosis to decrease in comparison with colitis group. 

The results of this study indicated that Enalapril alone and in combination with SSZ decreased inflammation and clinical symptoms of colitis induced by DSS.

Caspase 3 gene plays a role in the progression of degeneration and caspase 9 in apoptotic, necrotic, and lysosomal deaths, and after the nerve damage, This study aimed to determine the neuroprotective effects of hydro alcoholic extract and fractions of Agrimonia eupatoria plant on neuron density and the change in the expression of caspase 3 and 9 genes 36 male Wister rats weighing were divided to 6 groups including control, compression, treatment A (compression + hydro alcoholic extract in dose of 75 mg/kg), treatment B (compression + ethyl acetate fraction in dose of 75 mg/kg dose), Treatment C (compression +N butanol fraction in dose of 75 mg/kg) and treatment D (compression + aqueous phase with dose of 75 mg/kg). In the control group, after anesthetizing of the rats, the muscle at the sciatic nerve site was split without nerve damage and in compression group and treatment groups; sciatic nerve of the right leg was subjected to compression for thirty seconds. The first intraperitoneal injection of the extract was performed immediately after compression of the nerve and the second injection was performed 7 days later. After twenty-eight days, the rats were subjected to the perfusion method and samples were taken from the lumbar spinal cord. Slides were stained with toluidine blue, the neuron density was measured using a dissector method and the stereology method and the results were compared by t-test and Anova analysis. Spinal cord samples were taken, Total RNA extracted, and cDNA was synthesized, and then, and the expression changes of caspase 3 and 9 genes in the samples were investigated. The results showed that neuronal density increased significantly in all treatment groups compared to the compression group (p < 0.001) and it is more in the n-butanol group than the other groups. The gene expression of Caspase 3 and 9 decreased in all treatment groups compared with compression group (p < 0.01). The extract of this plant can be effective in repairing the nervous system due to the presence of compounds such as tocopherol, which has anti-oxidant and anti-apoptotic effects.

Intestinal colitis, also known as ulcerative colitis, is an inflammatory bowel disease characterized by long-term inflammation and ulcers in the gastrointestinal tract. It has been suggested that the mucosal expression of angiotensin II (AT-II) is increased in colitis. This study aimed to examine the potential therapeutic effects of combination therapy with Enalapril, an angiotensin-converting enzyme inhibitor, and sulfasalazine (SSZ) in a murine colitis model.

Male C57BL/6 mice were divided into five groups: control group (distilled water), dextran sulphate sodium (DSS) group (colitis group) (1% DSS), SSZ group (positive control group) with 100 mg/kg/day, Enalapril alone group with 4 mg/kg/day, and Enalapril (4 mg/kg/day) + SSZ (100 mg/kg/day) group.

There was a significant reduction in the disease activity index among the mice receiving the combination of Enalapril and SSZ compared to the colitis group. Enalapril and SSZ treatment was associated with a lower reduction in colon length, decreased colon weight, spleen weight, and spleen-to-body weight in mice with colitis. Following DSS administration, Enalapril and SSZ also significantly decreased MDA levels, an oxidant marker, and increased total thiol, SOD, and CAT levels, as antioxidants. Additionally, mucosal damage, crypt loss, pathological changes, and inflammation scores decreased after treatment with Enalapril and SSZ in comparison with the colitis group. The combination of Enalapril and SSZ reduced colon collagen content and caused a decrease in fibrosis compared to the colitis group.

The results of this study indicated that Enalapril alone and in combination with SSZ decreased inflammation and clinical symptoms of colitis induced by DSS.

The current study aims to achieve synthesized selenium nanoparticles (Se-NPs) through a green chemistry route using sodium selenite (Na2SeO3) and Caccinia macranthera (C. macranthera) plant extract as stabilizing and reducing agents and to investigate the anticancer effects of the synthesized NPs.

The outcomes affirmed the successful production of the synthesized Se-NPs, as their spherical framework and particle size scale of 54 to 60 nm were exhibited by the images of FESEM/PSA. This spherical frame was also detected in the TEM images at a size of 11.5 nm. The inhibitory effect of Se-NPs was investigated on the proliferation of human liver cancer cells (Huh-7). Additionally, the effect of Se-NPs was studied on the expression of the implicated genes throughout the cell apoptosis using the Real-Time PCR technique. Also, the percentage of apoptotic cells was obtained using Annexin V/PI and DAPI kits. Finally, flow cytometry was exerted to determine the amount of produced ROS. 

The results of laboratory studies showed that Se-NPs can significantly reduce the survival of Huh-7 cancer cells in dosage and time-reliant behavior, while they have very little toxicity on normal L929 cells. Also, Se-NPs were able to induce apoptosis in liver cancer cells, which was observed along with the increased expression of Bax, p53, Caspase3, and Caspase 9 genes. In addition, Se-NPs increased the production of ROS in Huh-7 cells and led to an increase in oxidative stress in these cells. 

Therefore, these NPs can be used in clinical studies of liver cancer.

Harmine is an alkaloid from the carboline family, belonging to the harmal plant, which has extensive applications in traditional medicine, with numerous studies highlighting its anti-cancer effects. Since biological processes are influenced by electromagnetic fields, the current study examined the anti-cancer effects of harmine and low-frequency electromagnetic fields on the expression of COX2, VEGF, and MMP-2 genes in the A2780 cell line.

In this experimental-laboratory study, ovarian cancer cell lines were randomly divided into four groups: control, harmine at concentrations of 6, 12, 24, 48, 96, and 192 micromolar, low-frequency electromagnetic field with an intensity of 50 Gauss, and harmine at a concentration of 48 micromolar with a low-frequency electromagnetic field of 50 Gauss intensity. Their toxicity was assessed using the MTT assay, nuclear morphological changes by DAPI staining, apoptotic effects of these compounds by measuring nitric oxide (NO), and gene expression changes by Real-Time PCR. Quantitative data were analyzed the ANOVA statistical test at a P < 0.05 level.

Quantitative data comparison of this research indicated that harmine and a low-frequency electromagnetic field with an intensity of 50 Gauss caused a concentration-dependent reduction in the viability of ovarian cancer cells. Additionally, in the nitric oxide test, a significant decrease was found in the control group compared to the groups treated with a concentration of 48 micromolar and synergized with a 50 Gauss electromagnetic field (p<0.05). The expression of the aforementioned genes in treated cells showed a significant decrease. Treating ovarian cancer cells with harmine and its combined application led to significant nuclear morphological changes, including chromatin condensation, formation of apoptotic bodies, and wrinkling of the cell membrane.

The combined application of harmine and a low-frequency electromagnetic field induced apoptosis in A2780 cancer cells and resulted in the downregulation of COX2, VEGF-A, and MMP-2 gene expression. Consequently, the combined use of harmine with a low-frequency electromagnetic field, due to its effective cytotoxicity in inhibiting proliferation and inducing apoptosis, could be a suitable candidate for clinical studies.

Diabetes Mellitus is related to biochemical and physiological changes in the body. In this study, the effects of anthocyanin on blood biochemical factors related to diabetes in adult diabetic rats treated with streptococci were investigated.

In this study, 32 male Wistar rats were used, which were divided into four groups as follows: a) control group b) diabetic control group that received normal saline as a solvent c) group of rats Diabetics treated with 100 mg/kg of anthocyanin d) group of healthy rats that received 100 mg/kg of anthocyanin. To induce diabetes in the experimental groups, a single dose of 50 mg/kg streptozotocin (STZ) (Sigma) dissolved in 5 mm citrate buffer (pH = 4.5) was injected intraperitoneally. Then, fasting blood sugar, insulin serum level, and lipid profile serum level were measured.

fasting blood sugar and serum levels of TG and cholesterol increased significantly in the diabetic control group compared to the control group (p<0.05). Also, fasting blood sugar levels and serum TG and cholesterol levels in the groups treated with anthocyanin showed a significant decrease in comparison with the diabetic control group (P < 0.05). In all diabetic groups compared to the control group, the level of HDL and serum insulin decreased significantly (P < 0.05), and in the groups treated with anthocyanin compared to the diabetic control group, the level of HDL and serum insulin increased. Also, the weight of rats in the diabetic control group decreased significantly, and in the treatment groups with anthocyanin, the weight of the rats increased compared to the diabetic control group (p<0.05).

Anthocyanin can be effective on fasting blood sugar, serum level of insulin, serum level of fat profile and prevent biochemical damage caused by diabetes in diabetic rats treated with streptozocin.

In recent years, in vitro maturation (IVM) has become the focus of fertility maintenance, and infertility treatment. The aim of this study is development of oocytes during folliculogenesis and oogenesis is greatly influenced by the presence of BMP-7, BMP-15, and GDF-9 genes, which are present in exosomes generated from bone marrow stem cells.

In the experimental study, we investigated how exosomes obtained from bone marrow stem cells affected development and expansion of ovarian granulosa cells (GCs) in NMRI mice. In this in vitro experiment, bone marrow stem cells were isolated from mice’s bone marrow, and after identification, exosomes were recovered. Exosome doses of 100, 50, and 25 μg/ml were applied to GCs before using MTT assay to measure survival rates and quantitative reverse-transcription polymerase chain reaction (PCR) to measure expression of the BMP-7, BMP-15, and GDF-9 genes.

The results showed that the GCs treated with exosomes concentrations of 25, 50, and 100 μg/ml significantly increased bioavailability, growth and proliferation and it also increased expression level of BMP-7, BMP-15 and GDF-9 genes compared to the controls.

Findings of this study indicated that exosomes derived from bone marrow stem cells improved growth of GCs in NMRI mice and they were a good candidate for further clinical studies to improve quality of the assisted reproductive techniques.

Pancreatic cancer is one of the most deadly and aggressive cancers; Fluorouracil induces apoptosis and cell cycle arrest in cancer cells. In the present study; the effect of Fluorouracil on different stages of the cell cycle and the expression of genes involved in the internal pathway of apoptosis in the AsPC-1 cell line (human pancreatic cancer) were investigated. In order to do so, MTT assay was used to evaluate the cytotoxic effect of Fluorouracil on AsPC-1 cell proliferation; The type of induced cell death and cell cycle changes were investigated by flow cytometry; changes in the expression level of genes (BAX, Bcl-2, APAF-1, Caspase-3, Caspase-9, p53, p21) were examined by Real-time PCR. Quantitative data were analyzed at the significant level of (p<0.05). The MTT assay results showed that Fluorouracil decreased AsPC-1 cell proliferation in a concentration-dependent manner. The results of flow cytometry analysis showed that increased percentage of apoptotic cells in the treated cells; Fluorouracil induces S phase cell cycle arrest in AsPC-1 cells and reduced distribution in the G1 phase. The Real-time PCR results in treated cells showed an increase in the expression of genes in the mitochondrial apoptotic pathway as well as genes effective in regulating the cell cycle. Fluorouracil reduces cell proliferation and induces apoptosis by increasing the expression of genes involved in the Intrinsic apoptotic pathway in AsPC-1 cells; Fluorouracil also caused cell cycle arrest in these cells by regulating the (p53, p21) genes.

In this study the effects of paclitaxel and oxaliplatin on colon cancer cell line (HT29) and expression of apoptotic genes caspase 3, 9, and p53 were examined. Using the MTT method, the cytotoxicity of paclitaxel and oxaliplatin and synergic effect at different concentrations on the HT29 cell line was assessed. The IC50 of paclitaxel and oxaliplatin was determined.The expression level of caspase 3 and 9 was assessed using the Real-Time PCR method after the cells had been exposed to the IC50 concentration. Apoptosis of the cells was done using Annexin V/PI and DAPI staining. The treatment of cells revealed that paclitaxel and oxaliplatin at concentrations of 3.25 and 0.00062 µg/ml , respectively, have the most cytotoxic effects and its IC50 value was determined to be 12.5 µg/ml and 0.00016 and treatment groups at concentrations of 3.25 and 0.00062 µg/ml , respectively, decreased the cell viability and its IC50 value was determined to be 12.5 µg/ml and0.00016µg/m. The expression level of caspase 3 and 9 P53 was also increased in the treated colon cancer cell line. DAPI staining showed apoptosis in the simultaneous treatment groups with. Using Annexin V/PI reveals that 98 percent of the cells in the control group are healthy and a considerable number of the cells in the treated groups have undergone apoptosis. Is. It is clear that paclitaxel and oxaliplatin are effective options for treating colon cancer given their cytotoxicity and stimulation of the apoptotic process in colon cancer cell lines.

In developing countries, the prevalence of breast cancer has increased and is becoming a major global problem. Extensive research has been devoted to understanding the causes of breast cancer and creating new treatment methods for this disease. The canola plant is rich in sulfur-containing compounds responsible for its rich content of glucosinolates, pungent aroma, and flavor. This plant contains antioxidants such as vitamin C and E, carotenoids, and antioxidant enzymes such as catalase, superoxide dismutase (SOD), and peroxidase. This research aims to investigate the effect of canola oil nanoemulsion on the hematological factors of mice suffering from breast cancer with the TUBO cell line.

In this experimental research, the synthesis of nanoemulsion from canola oil was carried out, and its size and stability were confirmed. Then the TUBO cancer cells were cultured and injected into mice. The treatment was carried out with canola oil nanoemulsion with 1, 2 and 4% concentrations and homogenous with tamoxifen. Statistical analysis of data related to blood parameters was done by SPSS statistical software .One-way ANOVA and Tukey's test were used to compare the results between groups (p<0.05 was considered significant).

In the present study, the count of white blood cells in the cancer group increased significantly compared to the control group (control: 3167 ± 93, cancer: 8150 ± 676, P < 0.01). Furthermore, by performing the treatment and increasing the amount of Canola oil nanoemulsion, the amount of white blood cells decreased compared to the cancer group (4775 ± 1557 and P < 0.01). On the contrary, the count of red blood cells decreased from 7712000 ± 400000 in the control group to 5908000 ± 190000 in the cancer group (P < 0.001). Treatment with nanoemulsion corrected this change and increased the number of red blood cells to 6444000 ± 120000 (P < 0.05). Regarding hemoglobin and related parameters, no significant difference was observed between the control and the cancer groups and treatmentwith nanoemulsion and tamoxifen groups. The number of platelets in the cancer group showed a significant difference from the control group, and the treated groups showed significant changes = somewhat similar to the control group (control: 787000 ± 131243, cancer: 405250 ± 40034, treated with nanoemulsion: 633400 ± 48264 (P < 0.05).

The synthesized Canola oil nanoemulsion with the size below 50 nm and a zeta potential of about -30 has high stability and uniform dispersion. Cancer induction caused changes in the blood parameters of mice. The treatment with nanoemulsion improved the condition to the desired extent, which is probably related to the antioxidant compounds present in the Canola oil.

Cisplatin, as a chemotherapy drug, causes serious side effects in the advanced stages of the cancer. Recently, Artemisia has been considered for its bioactive compounds, anti-proliferative and anti-inflammatory effects. The aim of this study was to evaluate the anti-cancer and anti-metastatic effects of the methanolic extract of aerial organs of Artemisia and cisplatin, either alone or in combination, in human ovarian cancer cell line A2780. The viability of A2780 cells after treatment with Artemisia extract, cisplatin and their combination was evaluated by MTT assay and the alterations in the morphology of the cell nuclei were examined by DAPI staining. The induction of apoptosis was assessed by Annexin V test, cell migration and changes in expression levels of apoptotic genes (Bax and P53) and metastasis (MMP2 and MMP9) using real-time PCR. MTT test data showed that Artemisia extract, cisplatin and their combination decreased the viability of ovarian cancer cells. DAPI and Annexin V indicated the DNA fragmentation and increased percentage of cellular apoptosis in comparison with the control group. The migration and real-time PCR data showed a decline in thr cell invasion and expression of genes involved in metastasis (MMP2 and MMP9) in cancer cells while the expression of apoptotic genes (Bax and P53) was increased in the treated groups. The results of this study showed that while both Artemisia extract and cisplatin posses anti-proliferative effect, apoptotic and suitable anti-metastatic effects on their own in A2780 cell line, their combination have synergic effects and posses those desired properties in lower concentration of cisplatin, which can reduce the side effects of cisplatin in cancer treatment.

This study aimed to evaluate the effect of anthocyanin on oxidative stress, sperm, and testis structure in diabetic rats induced by streptozotocin (STZ).

In this experimental research, diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg). A total of 64 rats were assigned into four groups as follows: a control group, a diabetic control group, a diabetic group daily administrated with anthocyanin at a dose of 100 mg/kg, and a healthy group daily administrated with anthocyanin for 56 days. After intervention, all the rats were anesthetized, their blood samples were taken, and the serum levels of insulin, glucose, and oxidative stress markers were measured. Finally, the testicles were removed and histological parameters were assessed.

Treating diabetic rats with anthocyanin significantly improved the testis tissue damage, glucose, and insulin plasma levels (P = 0.001). Furthermore, the level of malondialdehyde (MDA) was up-surged and the serum levels of superoxide dismutase (SOD) and catalase (CAT) were reduced (P = 0.001). Also, anthocyanin administration (100 mg/kg BW) significantly rectified these parameters (P < 0.05).

Our results confirmed the antioxidant role of anthocyanin in improving the sperm parameters and testicular oxidative damage caused by diabetes.

Glutamine (Gln) is an essential amino acid with a wide range of cellular functions and is necessary for cell proliferation. It is usually added to the culture media in the form of L-glutamine, which is highly unstable and degrades in a temperature-dependent manner during the culture period. Although, Gln is beneficial for the cells, its degradation produces ammonia which is toxic and negatively affect cell culture. Pheochromocytoma cells (PC-12), originating from cancerous cells of the rat adrenal gland, are considered as a suitable model to study the differentiating effects of different factors. Previous studies showed the importance of Gln in the normal growth and differentiation of the cells. Alginate, is one of the biomaterials currently used as a natural scaffold for the induction of neuronal differentiation. In the present experimental research, the effect of stable and elevated levels of Gln on the growth and neuronal differentiation of PC-12 cells was compared under 2D- and 3D- (sodium alginate hydrogel beads) culture conditions. The cells’ viabilities were determined and compared between experimental groups using live/dead cell staining by Acridine orange/Propidium iodide (AO/PI), and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Furthermore, cells were stained using cresyl violet to detect neuronal Nissl bodies. The induction of differentiation was confirmed using immunocytochemical analysis of Nestin and β-tubulin III proteins and Cells’ nuclei were counterstained with 4′,6-diamidino-2-phenylindole (DAPI). Results showed that high concentration of Gln can induce neuronal differentiation in PC-12 cells under both 2D- and 3D- culture conditions and increases the expression of progenitor and mature neuronal markers Nestin and β-tubulin III, respectively.

Pancreatic cancer is one of the deadliest cancers related to the digestive system in the world. Due to the increasing resistance of cancer cells to chemotherapy and its side effects, there is a need for drugs with fewer side effects and natural origin. In this study, the effect of harmine combined with fluorouracil on apoptosis induction in pancreatic cancer cells (AsPC-1) and the expression of apoptotic genes was investigated.

In this experimental study, MTT assay was used to study the cytotoxic effects. Annexin V/propidium iodide test and DAPI staining method were used to determine the type of cell death. The expression of apoptotic genes (P53, Bax, Caspase-3, and Caspase-9) was measured by real-time PCR. The data were analyzed using one-way ANOVA in SPSS software, version 16. The significance level was set at 0.05.

The results of MTT assay showed that the use of harmine at 20 μg/mL concentration combined with 10 μg/mL fluorouracil significantly reduced the growth (IC50) of AsPC-1 cells. The results of DAPI staining and annexin V/propidium iodide test showed the induction of apoptosis in treated samples. In addition, the results of real-time PCR showed that the expression of BAX, P53, Caspase-3 and Caspase-9 genes increased in the treated groups compared to the control group.

The combined use of harmine and fluorouracil can induce apoptosis in pancreatic cancer cells due to high cytotoxicity and reduce the concentration of chemotherapy drugs. Therefore, this method can be used along with other treatment methods for pancreatic cancer.

Ovarian cancer has the highest mortality rate among all genital malignancies. It is the sixth cancer in the western world that has no symptoms at all in the early stages. One of the genes that is highly expressed and inhibited in cancer is the Cox gene. The aim of this study was to evaluate ovarian cancer in early stages, evaluation of Cox gene expression and SGPT and SGOT enzymes, and also investigated the treatment of different concentrations of nettle extract. In this experimental study, hydroalcoholic extract of nettle leaf, stem and root was prepared and doses of 75 and 250 mg/kg body weight were prepared. DMBA was used to induce ovarian cancer in mice. Blood samples were taken after 28 days to measure enzyme levels. Ovarian tissue was then separated, weighed and morphologically compared with other organs. RNA extraction, nanodrape, electrophoresis, cDNA synthesis, and gene expression analysis were performed. The results were evaluated by SPSS software. The results of SGOT enzyme assay showed that R250, S75 and T2 treatments had significant changes. The normal expression level of Cox gene was in the laboratory control (1.63) and the lowest gene expression was related to S75 treatment on day 28 and the highest expression was related to R75 on the same day. Cox gene expression changes and the SGOT enzyme can be used as a marker for early detection of ovarian cancer.

Alkaloids have anti-proliferative and apoptotic stimulatory effects on cancer cells. Harmine is also one of the important alkaloids that have been reported to have anticancer effects. The aim of this study was to investigate the effect of Harmine on apoptosis induction in human HT29 colon cancer cell line and expression alteration of apoptotic genes P53, Bax and Bcl-2. For this purpose, HT29 colon cancer cells were treated with different concentrations of harmine (0, 35, 45, 55, 65 μg/ml) for 24 hours. Then the cell viability was assessed using the MTT assay. Nuclear changes and chromatin condensation were investigated by DAPI staining. Also, apoptosis induction was determined by Annexin V-FITC testing and changes in P53, Bax and Bcl-2 genes expression was assessed by using Real Time PCR. The results showed that the concentration of Harmin reduced the viability of HT29 colon cancer cells. Also, the treatment of HT29 colon cancer cells with Harmin caused morphological changes in the cell nucleus, including chromatin condensation of the nucleus, the formation of apoptotic bodies, and the wrinkling of the cell membrane. All of these morphological features indicate apoptosis. The results of the Annexin test also confirmed this finding; with about 57% of the cells undergo apoptosis. On the other hand, the treatment of HT29 cancer cells with Harmin reduced the expression of Bcl-2 and at the same time increased the expression of P53 and Bax and, in general, reduced the ratio of Bcl-2 to Bax. As a result, Harmin can be used to treat colon cancer cells because of its cytotoxicity, which is effective in inhibiting cell prolifration and inducing apoptosis.

Gastric cancer is the second leading cause of cancer death worldwide. Artemisia absinthium is one of the genus Artemisia which has anti-inflammatory and anti-viral properties. In the present study investigated the ability of methanolic extract of A. absinthium alone and in combination with Taxol to induce apoptosis and inhibited cell migration in the AGS cell line. Investigating cytotoxic effect of combined A. absinthium extract with Taxol on the proliferation of AGS cells, were used MTT assay; DAPI staining and flow cytometry analysis were used to evaluate the ability to induce apoptosis in treated cells and cell migration test was used to evaluate the anti-invasive effect; Changes in the expression of apoptotic "p53-Caspase-3,9" and metastasis genes "MMP-2,9" were examined by real-time PCR. The MTT results showed that the combination of A. absinthium extract with Taxol inhibited the proliferation of AGS cells in a concentration-dependent manner, Morphological observations obtained from DAPI and results of flow cytometry showed an increase in the percentage of apoptotic cells in the treatment groups. The results of cell migration test showed a decrease in the invasive potential of AGS cells. The real-time PCR results showed an increase in the expression of apoptotic genes and a decrease in the expression of metastatic genes in the treatment groups. The results of this study showed that the combined use of A. absinthium extract with Taxol inhibits the proliferation of AGS cells and induces apoptosis and inhibits the ability to migrate.

Melanoma is the most serious kind of skin cancer which has significantly increased in recent decades, and the importance of its primary treatment is increased widely. Ficus carica leaves have various therapeutic impact such as anti-inflammatory, anti-proliferative and apoptotic activity.

Hence, regarding the F. carica effect on the treatment of various diseases, the present research was conducted to identify the effect of methanolic extract of F. carica leaf on apoptosis induction in B16F10 melanoma cancer cells.

Cell survival was estimated by MTT assay after treatment of B16F10 cells in various concentrations of F. carica leaf extract (150, 250, 350, 450, 550, 650, 750 and 850 µg /mL) for 24 and 48 h. Cell apoptosis was analysed by AO/PI and DAPI staining, Annexin V/Propidium Iodide flow cytometry. Moreover, Real-time PCR was utilized to evaluate the expression of apoptotic genes including p53, Bax, caspase-3 and caspase-9 genes.

MTT assay results indicated that methanolic extract of F. carica leaf prevented the proliferation of B16F10 cells in a dose and time dependent manner. AO/PI staining results showed an elevation in apoptotic cells in treated groups and DAPI indicated that F. carica extract resulted in chromatin condensation and fragmentation. Annexin V revealed the increasing percentage of apoptotic cells after treatment. In addition, the up-regulation of apoptotic genes confirmed the apoptosis inducing potential of F. carica leaves in B16F10 cells by Real-time PCR.

Thus, methanolic extract of F. carica leaves could be suggested as an effective anti-cancer agent for further studies on melanoma cancer.

Lung cancer is the most common cause of cancer death worldwide. Berberine as a herbal alkaloid has antioxidant, anti-cancer and anti-tumor properties. Cisplatin is a potent inducer of apoptosis in most types of cancer cells. In the present study, investigated the ability of berberine alone and in combination with cisplatin to induce apoptosis in the Calu-6 cell line (human lung cancer cell line).

In this experimental study, MTT assay was used to evaluate the cytotoxic effects of combination of berberine with cisplatin on Calu-6 cell proliferation; DAPI staining and annexin V-FITC assay were also used to evaluate apoptosis in treated cells; changes in the level of transcripts of BAX, Caspase 3,9, p53 genes were examined by real-time PCR. Quantitative data were analyzed by one-way ANOVA at a significant level of P<0.05.

The MTT assay results showed that the combination of berberine with cisplatin inhibits the proliferation of Calu-6 cells in a concentration- and time-dependent manner. Morphological observations obtained from DAPI staining method and annexin V-FITC assay showed an increase in apoptotic cells in the treatment groups. The real-time PCR results showed an increase in the expression of transcripts of BAX, Caspase 3,9, p53 genes in the treatment groups.

The results of this research showed that the concomitant use of berberine with cisplatin inhibits the proliferation of Calu-6 cells and induces apoptosis in these cells.

Nowadays, researchers have made extensive efforts to find new treatments for nerve damage. Meanwhile, the role of exosomes in cell-cell communication is considered to be a new mechanism. Exosomes can act as suitable differentiating agents. The aim of this study was to investigate the differentiating effect of cerebrospinal fluid-derived exosomes on adipose mesenchymal stem cells in alginate hydrogel. Exosomes were extracted from the cerebrospinal fluid by ultracentrifugation and were then identified by atomic force microscopy (AFM), SEM and DLS technique. In addition, Adipose Mesenchymal Stem cells in alginate hydrogel were treated with different concentrations of exosomes. Cell survival was assessed by MTT and Acridine Orange/Ethidium Bromide methods. Cell differentiation was processed by immunocytochemistry and Real-Time PCR. Examinations confirmed the presence of exosomes with an approximate size of 70 nm. Cell survival results indicate that he ability of cells to survive and proliferate during 14 days. Also, the expression of MAP2 proteins (microtubule-associated protein 2) and Nestin (intermediate filament protein) was confirmed by immunocytochemistry. The results of Real Time - PCR showed that during the seventh and fourteenth days the expression level of MAP2 gene increased and the expression of Nestin gene showed a significant decrease compared to the control group. This study showed that exosomes extracted from cerebrospinal fluid can cause neuronal differentiation of Adipose mesenchymal stem cells in alginate hydrogel scaffolds.

Cancer is the leading cause of death after cardiovascular diseases, and accidents. Nowadays, researchers are increasing their efforts to use treatments with minimal side effects and make an attempt to use traditional medicine and herbal remedies. AnbarNesara is a seemingly worthless substance found in traditional medicine used in the treatment of many diseases. The aim of the present study was to evaluate the cytotoxic effects of the smoke from the burning of AnbarNesara on liver cancer cells and to investigate the genes expression changes of P53 and CYP2E1.

In the current experimental study, first Anbarnsara was collected from Dargaz region in spring and then the smoke from its fuel was collected in cold propyleneglycol. The amount of smoke in the solvent was calculated. Then, liver cancer cell line (HEPG2) and normal cell line were cultured. Cytotoxicity tests and morphological studies were performed and IC50 value was calculated. RNA extraction, cDNA synthesis, and Real Time PCR were performed to evaluate the expression of P53 and CYP2E1 genes. The results were analyzed using t-test and ANOVA at a significance level of P <0.05.

The results of morphological studies and toxicity test indicated that smoke from AnbarNesara fuel at a concentration of 58.5 mg/ml increases cancer cell mortality (IC50=48.79) compared to that in the control group (P <0.05). In the study of gene expression, while the concentration of 117 mg increased the expression of CYP2E1 gene, the P53 gene increased at the concentration of 58.5 (P <0.05).

The smoke from burning Anbarnsara seems to have a lethal effect on liver cancer cells. Duration and concentration are significant in this effectiveness.

In children with lymphoblastic leukemia (ALL), cancerous metastasis to the central nervous system (CNS) is common, but there is insufficient information on this metastasis and cancer progression process. Further, the role of exosomes on cancer growth and metastasis has been the attention of many studies. Because the astrocytes involve in the blood-brain barrier and stay in contact with peripheral blood , we investigated the effect of exosomes derived Nalm6 cell line on astrocytes from human brain fetal tissue.     In this in vitro study, exosomes were isolated from the supernatant of Nalm6 cell line by centrifugation and identified by DLS, AFM and FE-SEM methods. Astrocytes were isolated from human fetal brain tissue cells and expanded and identified by GFAP antibody with immunocytochemistry. Astrocytes were treated with different concentrations of exosomes (i.e., 5, 10, 30, and 50 µg/ml),. Proliferation and migration were assessed with Trypan blue staining and scratch methods, respectively. To define tumorogensis changes in astrocytes treated by exosomes, the expression of MMP9, P53, and Cox2 genes were investigated by Real-Time PCR. According to the DLS results, the size of exosomes was about 43 nm. AFM and FE-SEM imaging indicated these exosomes have a spherical shape. Our results showed that the proliferation of astrocytes significantly increased when treated with 50 µg/ml of exosomes.Therefore, the concentration of 50 µg/ml was considered for further experiments. Astrocyte migration was significantly increased compared to the control group. Finally, our results showed tumorogenesis changes in astrocytes by increasing the expression of MMP9 and Cox2 and decreasing the expression of p53 at mRNA level. Based on our in vitro study, exosomes derived from ALL as a peripheral tumor can change the behavior of astrocytes as a target for metastasis. Further investigations on this topic are warranted to shed light on metastatic mechanisms.

 Ovarian cancer is the leading cause of death caused by genital cancers. One of the most common treatments for this type of cancer is chemotherapy by cisplatin, which induces apoptosis in cancer cells. Apoptosis is a type of physiological cell death. Cisplatin chemotherapy usually has several side effects and cellular resistance to cisplatin is a common incidence. In order to overcome these problems, the use of combination therapies using natural substances has been considered. Fisetin is a flavonoid with anti-cancer activity which induces apoptosis</span>. In this study, the apoptosis induced by cisplatin along with Fisetin in cisplatin-resistant ovarian cancer cell line (A2780) was investigated.

  In the present experimental study, the effect of combined use of Fisetin and cisplatin on ovarian cancer cell lines (A2780) was investigated by using MTT assay. Cell death was also determined by DAPI, acridine orange/propidium iodide, and Annexin/PI assay. Apoptotic gene expression of Bax</em>, BCL-2</em>, caspase 3</em>, and caspase 9</em> was also assessed by real time PCR.

 The results of MTT assay indicated that the combined treatment of Fisetin and cisplatin effectively inhibits proliferation of A2780 cells. The results of DAPI staining showed that fragmentation of chromatin in cells occurred in the combined treatment. Acridine orange-propidium iodide staining and Annexin/PI staining showed an increase in the rate of apoptotic cells in cells under combined treatment. The results of the study regarding changes in gene expression also indicated that Bax</em> pro-apoptotic gene expression and BCL-2</em> anti-apoptotic gene expression increased in cells under treatment; moreover, gene expression of caspases 3</em> and 9</em> significantly increased as well.

According to the findings of this study, the combined use of cisplatin and Fisetin increases the induction of apoptosis in cisplatin-resistant ovarian cancer cells (A2780); therefore, the combined use of cisplatin and Fisetin can be considered a promising </span>strategy</span> in the treatment of ovarian cancer.